The Chemical Biology Core Facility consists of a multidisciplinary team of researchers whose aim is to initiate and advance collaborations within NIDDK chemical and biological laboratories. The goal of these partnerships is the discovery of new medicinal agents with therapeutic potential. The Chemical Biology Core Facility will advise, support and often develop each endeavor between laboratories, adding its expertise as needed, either in the synthetic development of novel molecules or in the pharmacological evaluation of existing compounds. Utilizing state-of-the-art methods in organic synthesis and pharmacological analysis the Chemical Biology Core Facility makes available numerous resources to support the laboratories of the NIDDK. Specifically, the CBCF has accomplished a number of research goals. They were instrumental in identifying the stereochemical requirement within a known inhibitor of O-GlcNAcase, an enzyme of critical importance within the post-translational modifications of proteins. The CBCF has successfully completed the synthetic production of several focus compound libraries aimed at targets such as the gonadotropin receptors, the TRH receptors, the adenosine receptors, O-GlcNAcase and O-GlcNAc transferase. The CBCF has gathered a compound repository that now boasts nearly 1000 diverse organic molecules for screening in a high throughput setting. Several NIDDK laboratories have relied on the CBCF to provide large amounts of known pharmacological active agents (such as the PPAR d activator GW 501516; the RXR ligand LG100268; the potent calcilytic NPS 2143) to enable NIDDK investigators to probe numerous aspects of cellular biology including transcription factor biology and calcium receptor modulation. The CBCF has completed the synthetic production of several oligopeptides to determine their selective binding to the muscurinic receptors. The CBCF has provided a 3H labeled cholestan derivative to facilitate the tracking of cholesterol within the cell and explored the total synthesis of a natural product with implications toward hypoglycemia.